Liang Junhua, Wang Qianqian, Wang Jiahao, Shao Yuxuan, Zhu Shuxiang, Wu Nianshuang, Huo Xiaolin, Zhang Guanghao, Lin Hua
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing, China.
J Alzheimers Dis. 2025 Jul;106(2):703-715. doi: 10.1177/13872877251344599. Epub 2025 Jul 1.
BackgroundRepetitive transcranial magnetic stimulation (rTMS) may be effective for Alzheimer's disease (AD) and mild cognitive impairment (MCI); however, the therapeutic efficacy varies significantly, highlighting the need for reliable biomarkers to predict treatment response. While rTMS may activates cortical white matter, the relationship between induced electric field (E-field) in this region and clinical outcomes remains unclear.ObjectiveThis study characterized the E-field in cortical gray matter (EF), cortical white matter (EF), and region-of-interest (EF) in the left dorsolateral prefrontal cortex (DLPFC), and explored their correlations with treatment efficacy in patients with MCI due to AD.MethodsThirty patients with MCI due to AD received 2-week rTMS treatment, with efficacy measured by Auditory Verbal Learning Test (AVLT) and a comprehensive neuropsychological battery. Responders were defined as those with >25% improvement in AVLT-immediate memory. Correlations between regional brain volumes and E-field magnitudes, and the correlations between E-field magnitudes and cognitive improvement, were analyzed. Predictive performance of E-fields for responder classification was evaluated.ResultsPronounced inter-individual variability in magnitudes of EF EF and EF was observed, partially explained by differences in regional brain volumes of DLPFC targeted area. Treatment responders exhibited significantly higher EF magnitude. EF positively correlated with AVLT-immediate memory improvement (R = 0.37) and predicted responder groups, achieving an area under the curve (AUC) of 0.76.ConclusionsE-field within cortical white matter in the DLPFC correlates with rTMS efficacy and predicts therapeutic response in MCI due to AD. Personalized stimulation protocols incorporating EF modeling may optimize treatment parameters.Trial registrationThis study is registered in the Chinese Clinical Trial Registry, number ChiCTR2200062564, date of registration: 2022-08-11.
背景
重复经颅磁刺激（rTMS）可能对阿尔茨海默病（AD）和轻度认知障碍（MCI）有效；然而，其治疗效果差异显著，这凸显了需要可靠的生物标志物来预测治疗反应。虽然rTMS可能激活皮质白质，但该区域的感应电场（E场）与临床结果之间的关系仍不清楚。
目的
本研究对左侧背外侧前额叶皮质（DLPFC）的皮质灰质（EF）、皮质白质（EF）和感兴趣区域（EF）中的E场进行了表征，并探讨了它们与AD所致MCI患者治疗效果的相关性。
方法
30例AD所致MCI患者接受了为期2周的rTMS治疗，疗效通过听觉言语学习测试（AVLT）和一套综合神经心理测试进行评估。反应者定义为AVLT即时记忆改善>25%的患者。分析了区域脑容量与E场强度之间的相关性，以及E场强度与认知改善之间的相关性。评估了E场对反应者分类的预测性能。
结果
观察到EF、EF和EF强度存在明显的个体间差异，部分原因是DLPFC目标区域的区域脑容量不同。治疗反应者的EF强度显著更高。EF与AVLT即时记忆改善呈正相关（R = 0.37），并能预测反应者组，曲线下面积（AUC）为0.76。
结论
DLPFC皮质白质内的E场与rTMS疗效相关，并可预测AD所致MCI的治疗反应。纳入EF建模的个性化刺激方案可能会优化治疗参数。
试验注册
本研究已在中国临床试验注册中心注册，注册号为ChiCTR22000
